This proposal seeks to identify specific neurobiologic actions in animals of acute and chronic exposure to and withdrawal from ethanol in blood levels of 200-400 mg/100 cc. Using electrophysiologic methods of extracellular unit recording, microiontophoretic administration, and electrical stimulation of selected pathways to identifiable target cells, ethanol will be investigated for selective actions on specific modes and sites of chemical synaptic transmission. With identification of significant ethanol actions, intracellular recordings and pharmacological perturbations will be used to determine the mechanism. Selected populations of cells known now, or to-be-characterized, as targets of combinations of noradrenergic, dopaminergic, serotonergic, or cholinergic input pathways will be used to evaluate selectivity of ethanol actions. Tests of the pathways and responses to iontophoretic administration of transmitters will be used to discriminate pre-synaptic and post-synaptic ethanol effects. For long-term exposure, repetitive intra-gastric administration for 5-7 days will be done according to procedures established by others for producing ethanol tolerance and physical dependence. In long-term ethanol treated animals, biochemical and histochemical assessment will be performed to evaluate the correlates of physiologic changes. Amino acid mediated synaptic and neuronal responses will also be evaluated for possible non-monoaminergic specific effects of ethanol. These experimental studies can provide a definitive characterization of the sites, mechanisms, and functional consequences of ethanol action in terms of specific sensitive neuronal pathways, and may help to pursue the biological basis of human alcoholism.